Culturing cells on flat plastic ware results in artificial two-dimensional sheets of cells. Normal cells in the human body experience a three-dimensional (3D) environment, completely surrounded by other cells, membranes, fibrous layers and adhesion proteins. Many whole cell-based assays in use today rely on flat, two-dimensional (2D) glass or plastic substrates that may not produce results characteristic of in vivo conditions. The value of 2D cellular assays is limited, because these assays do not mimic fully the response of cells in the 3D milieu present in a tissue in vivo. This may cause a lack of predictability of such 2D assays.
Various methods and materials have been studied for creating microenvironments. These efforts have so far been unpredictable, which indicates that not all relevant parameters which influence the development of 3D structures under culturing conditions are fully understood.
A system has been described wherein 3D synthetic polymer scaffolds are incorporated into standard cell culture dishes which support the formation of 3D cultures (Ke Cheng et al., Biomaterials 29 (2008), 2802-2812). These assays require 3D cell based vessels, which are fabricated by casting a thin layer of porous polymer scaffolds onto the glass bottom of a regular cell culture vessel. The 3D scaffolds are fixed on the vessels. With the aid of liquid handling robots, this 3D vessel fabrication can be applied to modify most currently available 2D cell culture vessels, such as 24-well-, 96 well- and 384-well plates for 3D cell culture and cell-based assay usage. A disadvantage of this approach is the dependency on existing well plates having a glass bottom. Moreover, these assays require many cells per well, a relatively large amount of medium and therefore also a large amount of test compounds.
It is therefore an objective of the invention to provide a multiwell system which has the following advantages:                Requires a minimum amount of test compounds and cells        Is suitable for high throughput screening        Enables 3D tissue culture formation        